Department of Neurology, Albert Einstein College of Medicine and the Montefiore Headache Center, Bronx, New York.
Headache Unit, Neurology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
JAMA Netw Open. 2022 Jun 1;5(6):e2215499. doi: 10.1001/jamanetworkopen.2022.15499.
Some patients with migraine, particularly those in primary care, require effective, well-tolerated, migraine-specific oral preventive treatments.
To examine the efficacy of atogepant, an oral, small-molecule, calcitonin gene-related peptide receptor antagonist, using 4 levels of mean monthly migraine-day (MMD) responder rates.
DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a phase 3, double-blind, placebo-controlled randomized clinical trial evaluated the efficacy and safety of atogepant for the preventive treatment of migraine from December 14, 2018, to June 19, 2020, in adults with 4 to 14 migraine-days per month at 128 sites in the US.
Patients were administered 10 mg of atogepant (n = 222), 30 mg of atogepant (n = 230), 60 mg of atogepant (n = 235), or placebo (n = 223) once daily in a 1:1:1:1 ratio for 12 weeks.
These analyses evaluated treatment responder rates, defined as participants achieving 50% or greater (α-controlled, secondary end point) and 25% or greater, 75% or greater, and 100% (prespecified additional end points) reductions in mean MMDs during the 12-week blinded treatment period.
Of 902 participants (mean [SD] age, 41.6 [12.3] years; 801 [88.8%] female; 752 [83.4%] White; 825 [91.5%] non-Hispanic), 873 were included in the modified intention-to-treat population (placebo, 214; 10 mg of atogepant, 214; 30 mg of atogepant, 223; and 60 mg of atogepant, 222). For the secondary end point, a 50% or greater reduction in the 12-week mean of MMDs was achieved by 119 of 214 participants (55.6%) treated with 10 mg of atogepant (odds ratio, 3.1; 95% CI, 2.1-4.6), 131 of 223 participants (58.7%) treated with 30 mg atogepant (odds ratio, 3.5; 95% CI, 2.4-5.3), 135 of 222 participants (60.8%) treated with 60 mg of atogepant (odds ratio, 3.8; 95% CI, 2.6-5.7), and 62 of 214 participants (29.0%) given placebo (P < .001). The numbers of participants who reported a 25% or greater reduction in the 12-week mean of MMDs were 157 of 214 (73.4%) for 10 mg of atogepant, 172 of 223 (77.1%) for 30 mg of atogepant, and 180 of 222 (81.1%) for 60 mg of atogepant vs 126 of 214 (58.9%) for placebo (P < .002). The numbers of participants who reported a 75% or greater reduction in mean MMDs were 65 of 214 (30.4%) for 10 mg of atogepant, 66 of 223 (29.6%) for 30 mg of atogepant, and 84 of 222 (37.8%) for 60 mg of atogepant compared with 23 of 214 (10.7%) for placebo (P < .001). The numbers of participants reporting 100% reduction in mean MMDs were 17 of 214 (7.9%) for 10 mg of atogepant (P = .004), 11 of 223 (4.9%) for 30 mg of atogepant (P = .02), and 17 of 222 (7.7%) for 60 mg of atogepant (P = .003) compared with 2 of 214 (0.9%) for placebo.
At all doses, atogepant was effective during the 12-week double-blind treatment period beginning in the first 4 weeks, as evidenced by significant reductions in mean MMDs at every responder threshold level. Higher atogepant doses appeared to produce the greatest responder rates, which can guide clinicians in individualizing starting doses.
ClinicalTrials.gov Identifier: NCT03777059.
一些偏头痛患者，尤其是在初级保健中，需要有效、耐受良好、专门针对偏头痛的口服预防治疗。
检查 atogepant 的疗效，这是一种口服小分子降钙素基因相关肽受体拮抗剂，使用 4 个平均每月偏头痛日（MMD）应答率级别进行评估。
设计、地点和参与者：这是一项为期 3 期、双盲、安慰剂对照随机临床试验的二次分析，于 2018 年 12 月 14 日至 2020 年 6 月 19 日在美国 128 个地点进行，参与者为每月有 4 至 14 个偏头痛日的成年人，使用 atogepant 进行预防性治疗偏头痛，患者分为 10mg 剂量组（n=222）、30mg 剂量组（n=230）、60mg 剂量组（n=235）和安慰剂组（n=223），每天 1 次，1:1:1:1 的比例给药，持续 12 周。
患者接受 10mg 的 atogepant（n=222）、30mg 的 atogepant（n=230）、60mg 的 atogepant（n=235）或安慰剂（n=223），每天 1 次，1:1:1:1 的比例给药，持续 12 周。
这些分析评估了治疗应答率，定义为参与者在 12 周双盲治疗期间达到 50%或更大（α控制的次要终点）以及 25%或更大、75%或更大和 100%（预先指定的附加终点）的平均 MMD 减少。
在 902 名参与者（平均[SD]年龄，41.6[12.3]岁；801[88.8%]名女性；752[83.4%]名白人；825[91.5%]名非西班牙裔）中，773 名被纳入改良意向治疗人群（安慰剂组 214 名；10mg atogepant 组 214 名；30mg atogepant 组 223 名；60mg atogepant 组 222 名）。对于次要终点，10mg atogepant 治疗的 214 名参与者中有 119 名（55.6%）、30mg atogepant 治疗的 223 名参与者中有 131 名（58.7%）、60mg atogepant 治疗的 222 名参与者中有 135 名（60.8%）和安慰剂治疗的 214 名参与者中有 62 名（29.0%）达到了 12 周平均 MMD 减少 50%或更多（P<.001）。在 12 周平均 MMD 减少 25%或更多的参与者中，10mg atogepant 组有 157 名（73.4%）、30mg atogepant 组有 172 名（77.1%）、60mg atogepant 组有 180 名（81.1%），而安慰剂组有 126 名（58.9%）（P<.002）。在 12 周平均 MMD 减少 75%或更多的参与者中，10mg atogepant 组有 65 名（30.4%）、30mg atogepant 组有 66 名（29.6%）、60mg atogepant 组有 84 名（37.8%），而安慰剂组有 23 名（10.7%）（P<.001）。在 12 周平均 MMD 减少 100%的参与者中，10mg atogepant 组有 17 名（7.9%）、30mg atogepant 组有 11 名（4.9%）、60mg atogepant 组有 17 名（7.7%），而安慰剂组有 2 名（0.9%）（P=.004）。
在第 4 周开始的 12 周双盲治疗期间，atogepant 对偏头痛有治疗作用，在每个应答阈值水平都显著降低了平均 MMD。较高的 atogepant 剂量似乎产生了最大的应答率，这可以指导临床医生个体化起始剂量。
ClinicalTrials.gov 标识符：NCT03777059。
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